Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.
Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.
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先前存在的针对 SARS-CoV-2 S2 的抗体会与共生肠道细菌发生交叉反应，并影响 COVID-19 疫苗诱导的免疫力。
DOI：
10.1080/19490976.2022.2117503
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发表时间：
2022-01
期刊：
影响因子：
12.2
通讯作者：
Wan, Yanmin
中科院分区：
文献类型：
--
作者：
Jia, Liqiu;Weng, Shufeng;Wu, Jing;Tian, Xiangxiang;Zhang, Yifan;Wang, Xuyang;Wang, Jing;Yan, Dongmei;Wang, Wanhai;Fang, Fang;Zhu, Zhaoqin;Qiu, Chao;Zhang, Wenhong;Xu, Ying;Wan, Yanmin
先前存在的SARS-CoV-2交叉反应抗体的起源及其对疫苗效力的潜在影响尚未完全阐明。在这项研究中，我们证明了S2是健康人和SPF小鼠中预先存在的S蛋白交叉反应抗体的主要靶点。在S2（1147-SFKEELDKYFKNHT-1160，P144）的连接结构域上鉴定了显性抗体表位，其可以被人和小鼠中预先存在的抗体识别。通过宏基因组测序和粪便细菌移植，我们证明了S2交叉反应抗体的产生与肠道细菌有关。此外，从未处理的SPF小鼠中分离出6种P144反应性单克隆抗体，并证明与从人和小鼠收集的肠道细菌交叉反应。利用LC-MS鉴定了多种具有交叉反应性的微生物蛋白，其中E.证实来源于大肠杆菌的HSP 60和HSP 70蛋白能够与分离的单克隆抗体之一结合。具有高水平的预先存在的S2交叉反应抗体的小鼠在用SARS-CoV-2 S DNA疫苗免疫后安装了更高的S蛋白特异性结合抗体，特别是针对S2。类似地，我们发现，预先存在的S2和P144特异性抗体的水平与两剂灭活SARS-CoV-2疫苗接种后的RBD结合抗体滴度呈正相关。总的来说，我们的研究揭示了预先存在的S2靶向抗体的替代来源，并揭示了肠道微生物群对宿主抗SARS-CoV-2免疫力影响的一个以前被忽视的方面。
The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.
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感染和疫苗接种后，在SARS-COV-2峰值蛋白上引起的交叉反应性抗体引起了保守的表位。
影响因子：
4.6
作者：
Geanes, Eric S.;LeMaster, Cas;Fraley, Elizabeth R.;Khanal, Santosh;McLennan, Rebecca;Grundberg, Elin;Selvarangan, Rangaraj;Bradley, Todd
通讯作者：
Bradley, Todd
影响因子：
7.8
作者：
Kim H;Seiler P;Jones JC;Ridout G;Camp KP;Fabrizio TP;Jeevan T;Miller LA;Throm RE;Ferrara F;Fredrickson RL;Lowe JF;Wang L;Odemuyiwa SO;Wan XF;Webby RJ
通讯作者：
Webby RJ
DOI：
10.1084/jem.20110363
发表时间：
2011-10-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liao HX;Chen X;Munshaw S;Zhang R;Marshall DJ;Vandergrift N;Whitesides JF;Lu X;Yu JS;Hwang KK;Gao F;Markowitz M;Heath SL;Bar KJ;Goepfert PA;Montefiori DC;Shaw GC;Alam SM;Margolis DM;Denny TN;Boyd SD;Marshal E;Egholm M;Simen BB;Hanczaruk B;Fire AZ;Voss G;Kelsoe G;Tomaras GD;Moody MA;Kepler TB;Haynes BF
通讯作者：
Haynes BF
影响因子：
5.9
作者：
Cobey S;Hensley SE
通讯作者：
Hensley SE
DOI：
10.1038/s41577-020-00460-4
发表时间：
2020-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Lipsitch M;Grad YH;Sette A;Crotty S
通讯作者：
Crotty S